Single Nucleotide Polymorphism in Patients with Moyamoya Disease

Abstract

Moyamoya disease (MMD) is a chronic, progressive, cerebrovascular occlusive disorder that displays various clinical features and results in cerebral infarct or hemorrhagic stroke. Specific genes associated with the disease have not yet been identified, making identification of at-risk patients difficult before clinical manifestation. Familial MMD is not uncommon, with as many as 15% of MMD patients having a family history of the disease, suggesting a genetic etiology. Studies of single nucleotide polymorphisms (SNPs) in MMD have mostly focused on mechanical stress on vessels, endothelium, and the relationship to atherosclerosis. In this review, we discuss SNPs studies targeting the genetic etiology of MMD. Genetic analyses in familial MMD and genome-wide association studies represent promising strategies for elucidating the pathophysiology of this condition. This review also discusses future research directions, not only to offer new insights into the origin of MMD, but also to enhance our understanding of the genetic aspects of MMD. There have been several SNP studies of MMD. Current SNP studies suggest a genetic contribution to MMD, but further reliable and replicable data are needed. A large cohort or family-based design would be important. Modern SNP studies of MMD depend on novel genetic, experimental, and database methods that will hopefully hasten the arrival of a consensus conclusion.

The Role of RNF213 4810G>A and 4950G>A Variants in Patients with Moyamoya Disease in Korea

“…At least 24 genetic changes in the RNF213 gene have been associated with moyamoya disease [ 31 , 32 ]. Three individual studies of MMD patients have revealed high frequencies of the same single base substitution (nonsynonymous mutation) as well as the c.14576G>A (p.R4859K) variant in RFP213 (a gene located in chromosome 17q) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

“…Three individual studies of MMD patients have revealed high frequencies of the same single base substitution (nonsynonymous mutation) as well as the c.14576G>A (p.R4859K) variant in RFP213 (a gene located in chromosome 17q) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The c.14576G>A in RNF213 is present in ~2% of East Asian populations, which is a relatively higher rate compared with Caucasians [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The RNF213 gene can be used as a biomarker to predict prognosis, as it has been reported that the RNF213 gene correlates with the early-onset and severe forms of MMD [ 33 ].…”

Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases

“…[1][2][3][4][5] Adults with MA typically present with ischemic (50-75%) or hemorrhagic (10-40%) stroke, whereas children may also present with transient ischemic attacks (including drop attacks). 1,3,[6][7][8] In 2013, Hishikawa et al reported that 9% of MA patients experience a type of stroke involving both ischemia and hemorrhage. 9,10 In hemorrhagic MA, recurrent hemorrhages were found to appear with an average annual incidence of 4.5% and are associated with increased mortality; smoking and hypertension are modifiable risk factors.…”

“…1,2 The initial efforts to elucidate the genetic markers of MA reflected this complexity, with a wide range of genes, chromosomes, and hereditary diseases reported to be potential markers (Table 1). [1][2][3][4][5][6]9, The current literature on familial MA suggests a low penetrance, autosomal dominant inheritance at loci on chromosomes 3p24.2-p26, 6q25, 8q23, 10q23.31, 12p12, and 17q25 (Table 1). 6,7,16,40,51,52,68,73,93 Polymorphisms of PDGFRB, MMP3, TIMP2, RNF213, TGFB1, RPTOR, and NOS3 genes may be associated with MA (Table 1).…”

“…The broad classes of proteins linked to MA as a result of hypothesis-driven biomarker discovery include enzymes, growth factors, transcription factors, adhesion molecules, inflammation and coagulation peptides, immune-related factors, biomarker candidates, and gene mutation products (Table 2). 2,5,6,9,[15][16][17][18][19][20][21][22][23][24]38,39,[45][46][47]49,50,52,[54][55][56][59][60][61][62][63][64][65][66][67][68][69][70][71][76][77][78][79][87][88][89][90][91][92]106,…”